3,3',4,4'-Tetrachlorozaobenzene (TCAB) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB), two environmental contaminants derived from microbial degradation of chloroanilide herbicides, have recently been found to cause outbreaks of chloracne among chemical plant workers. Various toxicological studies will be conducted in vivo and in vitro to assess the potential health hazards associated with these two agents. Changes in the general body health of Sprague-Dawley rats chronically exposed to TCAB and TCAOB will be investigated via pathological and clinical examinations, and the study of biochemical effects. Potential genetic toxicity (carcinogenicity and teratogenicity) will be also examined by using short-term toxicity testings. Pharmacokinetic profiles of TCAB and TCAOB including the nature of metabolites will be studied in rats and monkeys. In the second phase of the proposed research, the biochemical mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), specifically with regard to the "wasting syndrome", will be explored. Parallel experiments using TCAB and TCAOB will be conducted with special emphasis on the cellular energy metabolism. Rats will be orally administered a single LD50 dose of TCDD or TCAB/TCAOB. Changes in the hepatic gluconeogenesis and fatty acid metabolism will be studied to gain insight into the biochemical defect(s) ultimately responsible for the debilitation of intoxicated animals. The validity of any tentative biochemical hypothesis will then be assessed by the use of genetically obese (ob/ob) mice.